Our laboratory is evaluating a rotavirus vaccination strategy in infants and young children that involves the use of an animal rotavirus strain of rhesus rotavirus origin in combination with three human rotavirus- rhesus rotavirus reassortant strains to form a quadrivalent vaccine. This approach relies on the induction of antibody to the rotavirus outer capsid protein VP7. It was adopted in an attempt to achieve protection against each of the four medically important VP7 rotavirus serotypes. If the desired level of protection is not achieved by this vaccine, we are considering two major alternative strategies: (i) the use of one or more cold-adapted human rotavirus mutants which would possess the human rotavirus VP4 (whereas the quadrivalent vaccine possesses the rhesus rotavirus VP4), an important outer capsid protein that also induces neutralizing antibodies and may be important in the induction of heterotypic immunity; and (ii) replacement of at least a single gene of a human rotavirus strain or of a human rotavirus x human rotavirus reassortant, that is associated with virulence with that of a bovine rotavirus strain, thus preserving the VP4 and VP7 specificities of the human rotavirus strain. It is important to identify an experimental animal that develops diarrhea following oral administration of a virulent human rotavirus strain in order to determine if either of these approaches yield viruses that are attenuated. Previously, we induced rotavirus diarrhea, and virus shedding and a serologic response to rotavirus in one of two chimpanzees that were given a virulent VP7 serotype human rotavirus strain by the alimentary route. Last year we administered a cold-adapted (26 degrees C) human rotavirus reassortant that possesses ten genes (including VP4) from human strain Wa and one gene encoding VP7 from human strain DS-1 (a VP7 serotype 2 strain). The chimpanzee did not develop illness or shed rotavirus. Serologic study completed this reporting period indicated that this chimpanzee failed to develop an antibody response to rotavirus.